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Disruption of P2RY5, an orphan G protein–coupled receptor, underlies autosomal recessive woolly hair

Nature Genetics volume 40, pages 335–339 (2008)Cite this article

Abstract

The genetic determinants of hair texture in humans are largely unknown. Several human syndromes exist in which woolly hair comprises a part of the phenotype; however, simple autosomal recessive inheritance of isolated woolly hair has only rarely been reported1,2. To identify a gene involved in controlling hair texture, we performed genetic linkage analysis in six families of Pakistani origin with autosomal recessive woolly hair (ARWH; OMIM 278150). All six families showed linkage to chromosome 13q14.2–14.3 (Z = 17.97). In all cases, we discovered pathogenic mutations in P2RY5, which encodes a G protein–coupled receptor and is a nested gene residing within intron 17 of the retinoblastoma 1 (RB1) gene. P2RY5 is expressed in both Henle's and Huxley's layers of the inner root sheath of the hair follicle. Our findings indicate that disruption of P2RY5 underlies ARWH and, more broadly, uncover a new gene involved in determining hair texture in humans.

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Figure 1: Phenotype and fine mapping of ARWH on chromosome 13q14.2–14.3.
Figure 2: Identification of mutations in P2RY5.
Figure 3: Structure of P2RY5 and positions of the mutations.
Figure 4: P2RY5 expression in the human hair follicle.

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Acknowledgements

We are grateful to the family members for their participation in this study, and to H. Lam and M. Zhang for technical assistance. We appreciate the collaboration and discussions with R.M. Bernstein, H. Bazzi, V. Luria and K. Fantauzzo. We thank L. Langbein and J. Schweizer (Heidelberg) for generously sharing antibodies. We thank S. Ishii for discussions about P2RY5. This work was supported in part by US Public Health Service National Institutes of Health grant R01AR44924 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (to A.M.C.).

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Authors and Affiliations

  1. Department of Dermatology, Columbia University, College of Physicians & Surgeons, 630 West 168th Street, VC15 204a, New York, 10032, New York, USA

    Yutaka Shimomura, Muhammad Wajid, Yoshiyuki Ishii, Lynn Petukhova & Angela M Christiano

  2. Department of Biochemistry & Molecular Biophysics and Department of Ophthalmology, Columbia University, College of Physicians & Surgeons, 635 West 165th Street, Ninth Floor, New York, 10032, New York, USA

    Lawrence Shapiro

  3. Department of Genetics, Rutgers University, 145 Bevier Road Life Sciences Building, Room 128, Piscataway, 08854, New Jersey, USA

    Derek Gordon

  4. Department of Genetics & Development, Columbia University, College of Physicians & Surgeons, 701 West 168th Street, Room 1602, New York, 10032, New York, USA

    Angela M Christiano

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  1. Yutaka Shimomura
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  2. Muhammad Wajid
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  3. Yoshiyuki Ishii
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Contributions

The study was designed and supervised by A.M.C. Laboratory work and phenotyping and pedigree ascertainment were performed by Y.S., Y.I. and M.W.; statistical analyses were performed by L.P. and D.G.; clinical observations were made by M.W., Y.S. and A.M.C.; molecular modeling of P2RY5 mutations was performed by L.S.; and Y.S., L.P. and A.M.C. contributed to the preparation of the manuscript.

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Correspondence to Angela M Christiano.

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Supplementary Figures 1–5, Supplementary Table 1, Supplementary Note, Supplementary Methods (PDF 2063 kb)

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Shimomura, Y., Wajid, M., Ishii, Y. et al. Disruption of P2RY5, an orphan G protein–coupled receptor, underlies autosomal recessive woolly hair. Nat Genet 40, 335–339 (2008). https://doi.org/10.1038/ng.100

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